56 results about "Estrogen Receptor Modulators" patented technology

A method for preventing, diagnosing, or treating a condition mediated by an estrogen receptor by administering to a patient in need thereof an effective amount of a compound of formula I, II, or a combination thereof: wherein R1, R3, R4, and R5 are independently selected from H, OH, and ORa; R2 is selected from H, OH, and (C═O)(C1-7)alkyl; Ra is (C1-7)alkyl or (C═O)(C1-7)alkyl; or a derivative of the compound selected from N-oxide derivatives, prodrug derivatives, protected derivatives, isomers, and mixtures of isomers of the compound; or a pharmaceutically acceptable salt or solvate of the compound or the derivative. Compounds of formula I and II and pharmaceuticals compositions thereof are also presented.

The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or prevention of a variety of conditions related to estrogen functioning including: bone loss, bone fractures, osteoporosis, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of LDL cholesterol, cardiovascular disease, impairment of cognitive functioning, cerebral degenerative disorders, restenosis, gynecomastia, vascular smooth muscle cell proliferation, obesity, incontinence, and cancer, in particular of the breast, uterus and prostate.

The present disclosure provides methods for preventing or treating illness, improving responsiveness to immunization, and improving the efficacy of gene therapy in a patient by disrupting sex steroid signalling in the patient, wherein the bone marrow and other immune cell functionality is improved without, prior to, or concurrently with, thymic regeneration. In some embodiments, sex steroid signalling is interrupted or ablated in the patient by the administration of LHRH agonists, LHRH antagonists, anti-LHRH receptor antibodies, anti-LHRH vaccines, anti-androgens, anti-estrogens, selective estrogen receptor modulators (SERMs), selective androgen receptor modulators (SARMs), selective progesterone response modulators (SPRMs), ERDs, aromatase inhibitors, or various combinations thereof.

A method for selecting a breast cancer patient for therapy with an agent that reduces production of angiotensin II, for example an ACE inhibitor or renin inhibitor, comprises (a) determining whether the cancer comprises a tumor that is estrogen receptor positive (ER+) and (b) selecting the patient for such therapy only if the cancer is determined to comprise an ER+ tumor. A method for treating breast cancer in a patient further comprises (c) administering to the patient, if so selected, an agent that reduces production of angiotensin II, for example an ACE inhibitor or renin inhibitor. A method for treating a breast tumor in a patient having SERM-resistant ER+ breast cancer comprises administering to the patient an agent that reduces production of angiotensin II, for example an ACE inhibitor or renin inhibitor. A therapeutic combination useful in treatment of a breast tumor comprises an agent that reduces production of angiotensin II, for example an ACE inhibitor or renin inhibitor, and a second agent that comprises (a) an aromatase inhibitor or (b) an estrogen receptor modulator or antagonist.

The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or prevention of a variety of conditions related to estrogen functioning including: bone loss, bone fractures, osteoporosis, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of LDL cholesterol, cardiovascular disease, impairment of cognitive functioning, cerebral degenerative disorders, restenosis, gynecomastia, vascular smooth muscle cell proliferation, obesity, incontinence, and cancer, in particular of the breast, uterus and prostate.

The present invention is directed toward methods for treating vasomotor symptoms, (e.g., hot flashes and night sweats) in a patient in need thereof comprising administering a SERM as described herein.

Substituted benzoxazine and 3,4-dihydrobenzoxazine derivatives possessing activity as estrogen receptor beta (ERβ) modulators are provided which have the structure of formula I wherein the substitutents are as described herein.In addition, a method is provided for preventing, inhibiting or treating the progression or onset of pathological conditions associated with the estrogen receptor and to pharmaceutical compositions containing such compounds.

The present invention relates to compounds of formula (I): wherein R1 and R2 represent hydrogen or deuterium atoms; R3 represents a hydrogen atom or a -COOH, a -OH or a -OPO(OH)2 group; R4 representsa hydrogen atom or a fluorine atom; R5 represents a hydrogen atom or a -OH group; wherein at least one of R3 or R5 is different from a hydrogen atom; when R3 represents a -COOH, -OH or -OPO(OH)2 group, then R5 represents a hydrogen atom; when R5 represents a -OH group, then R3 and R4 represent hydrogen atoms; and R6 is selected from an optionally substituted phenyl, heteroaryl, cycloalkyl or heterocycloalkyl group. The invention also relates to the preparation and to the therapeutic uses of the compounds of formula (I) as inhibitors and degraders of estrogen receptors, useful especially in thetreatment of cancer.

Methods for treating hormone associated conditions, such as endometriosis, uterine leiomata, ovarian cancer, breast cancer, or vaginal bleeding, using LHRH antagonists and selective estrogen receptor modulators are disclosed. The methods include administering to a subject a combination of an LHRH antagonist and a selective estrogen receptor modulator. Pharmaceutical compositions and kits for use in the methods of the invention are also provided.

The invention relates to an acrylic acid derivative, a preparation method thereof and medical application of the acrylic acid derivative. Particularly, the invention relates to the acrylic acid derivative as shown in a general formula (I) defined in the description, the preparation method thereof, a pharmaceutical composition containing the derivative and application of the derivative serving an estrogen receptor modulator for treating estrogen receptor mediated or dependent diseases or symptoms, and the disease of a breast cancer is particularly preferable. All substituents of the formula (I) are the same as the definition in the description.

The disclosure provides a method of treating a mammal afflicted with an age-related disorder, comprising administering to the mammal a combination of liver X receptor (LXR) modulator and estrogen receptor (ER) modulator, in an amount effective to treat the mammal. Further disclosed are the LXR modulators and ER modulators used in the combination therapy.

The invention relates to a tetrahydroisoquinoline derivative, and a preparation method and medical application thereof. Particularly, the invention relates to the tetrahydroisoquinoline derivative asshown in a general formula (I), the preparation method of the tetrahydroisoquinoline derivative, a pharmaceutical composition containing the tetrahydroisoquinoline derivative, the application of the tetrahydroisoquinoline derivative as an estrogen receptor modulator, and the application of the tetrahydroisoquinoline derivative in preparation of drugs for treating estrogen receptor mediated or dependent diseases or symptoms. Each substituent in the general formula (I) is as defined in the specification.

This invention provides estrogen receptor modulators of formula: (I), having the structure wherein, R<1>, R<2>, R<3>, R<4>, R<5> and R<6> are as defined in the specification, or a N-oxide thereof or a pharmaceutically acceptable salt thereof or a prodrug thereof.

Certain embodiments of the invention provide methods of selecting a mutant plant cell that overproduces a compound that activates an estrogen receptor (ER) beta but does not activate an ER alpha.

The invention belongs to the technical field of medicines, and relates to a phenylindole derivative and application thereof.The phenylindole derivative comprises stereisomer and pharmaceutically-applicable salt of a phenylindole compound and has the structural formula (please see the formula in the description).The phenylindole derivative and the acid-added pharmaceutically-applicable salt of the phenylindole compound can be used in cooperation with existing medicines or used independently as an estrogen receptor regulator for treating or preventing various diseases related to estrogen functions such as bone loss, fractures, bone rarefaction, hectic fever, LDL cholesterol level rise, cardiovascular diseases, cognitive deficits, brain degeneration diseases, anxiety, depression caused by estrogen deficiency, sexual dysfunction, hypertension, retinal degeneration, cancers and especially osteoporosis.

The invention belongs to the technical field of medicine and relates to a 1,4-dihydrobithiophene [3', 2': 5, 6] bithiapyran [4, 3-c] pyrazol-3-carboxylic acid derivative and application thereof used as an estrogen receptor, in particular to a 1,4-dihydrobithiophene [3', 2': 5, 6] bithiapyran [4, 3-c] pyrazol-3-carboxylic acid derivative and a pharmaceutically acceptable salt, or a stereoisomer thereof and a prodrug as well as a pharmaceutically acceptable vector in compatibility or a diluent used as an estrogen receptor. The structural general formula of the derivative is disclosed in the specification, and in the structural formula, n R1 can be independently selected from a substituted or unsubstituted amido group, and R2 can be independently selected from H or an acetyl group. The derivative can be used for treating and preventing various diseases related to estrogen functions, such as diseases related to estrogen deficiency, estrogen sensitive cancer and hyperplasia, endometriosis, uterus myoma and osteoarthritis. Compounds or compositions of the derivative can also be independently used or combined with progestogen or a hormoneantagonist as a contraceptive.

The invention provides an ethylene derivative represented by a formula I. Serving as selective estrogen receptor modulators (SERMs), the ethylene derivative can be used for preventing and / or treating diseases or disease symptoms influenced by selective estrogen receptor modulation. The formula I is shown in the specifications.

The present invention relates to an estrogen receptor regulator of a formula (I) or a pharmaceutically acceptable salt thereof. The compounds can combine with the estrogen receptor alpha to produce the anti-breast cancer function and produce regulation function in uterus and other parts at the same time. The compounds have strong function of combining with the estrogen receptor alpha in vitro, and can effectively antagonize the combination of estrogen and the estrogen receptor alpha, thus treating breast cancer caused by excessive estrogen, while playing the role of regulating in the uterus and other parts.

This invention relates to novel 4,5-dihydroisoxazoles of formula (I), to their use as estrogen receptor modulators, and to methods of their preparation.

The invention belongs to the technical field of medicine, and relates to piperazinyl-containing indole derivatives and medical application thereof. The phenyl indole derivatives comprise stereomers and pharmaceutically applicable salts of the compounds, and the structural general formula is disclosed in the specification. The piperazinyl-containing indole derivatives and pharmaceutically applicable acid-added salts of the compounds can be mixed with the existing drug or independently used as an estrogen receptor regulator for treating or preventing various estrogen-function-related diseases, such as bone loss, fracture, osteoporosis, hectic fever, LDL cholesterol level increase, cardiovascular diseases, cognitive impairment, brain degeneration diseases, anxiety, depression caused by deficiency of estrogen, sexual disorder, hypertension, retinosis and cancer, and especially osteoporosis.

A topical application formulation of estrogen and estrogen analogs or other estrogen receptor modulators is disclosed for the treatment of primary or secondary dry eye syndrome (also known as keratoconjunctivitis sicca (KCS)). Preferred formulations include 17-β-estradiol and its derivatives in lipid, liposomes, polymers, or aqueous or non-aqueous vehicles for the topical treatment of the ocular surface tissues particularly as time-release or micro-dose formulations. These formulations may also be useful in treating other conditions where KCS may occur, such as post-operative refractive surgery and corneal transplant patients.

Described herein are methods and compositions for treating an ER-related disease condition characterized by a mutation in the ESR1 gene by administering an estrogen receptor modulator. Also described herein are methods of treating hormone resistant-estrogen receptor (ER) positive breast cancers characterized by a mutation in the ESR1 gene by administering an estrogen receptor modulator.

The invention relates to a drug combination containing pratensein and / or prunetin, which has the effects of preventing and treating cardiovascular systems, osteoporosis and the like via the effects ofselective estrogen receptor modulators widely distributed in the bodies. The combination can be used for preparing the drugs for treating cancers and lead compounds. The combination can be orally taken by the patients or be applied to the patients who need the treatment by nasal inhalation or in an external rectal, parenteral or local manner. The daily dose of the combination is 1mg-4mg / kg and the combination can be applied once or more times. The combination can be prepared into solid preparations, liquid preparations, creams, ointments, patches, spraying agents, subcutaneous implants and the like, and can be especially prepared into sustained release tablets, coated tablets and the like having effects on intestinal canals.

Described herein are methods and compositions for treating an ER-related disease condition characterized by a mutation in the ESR1 gene by administering an estrogen receptor modulator. Also described herein are methods of treating hormone resistant-estrogen receptor (ER) positive breast cancers characterized by a mutation in the ESR1 gene by administering an estrogen receptor modulator.

This invention is a benzothiophene estrogen receptor modulator or its pharmaceutically acceptable salt, N-oxide, isotopic derivative or prodrug thereof or a pharmaceutically acceptable composition thereof to treat an estrogen-related medical disorder. The invention also includes a combination thereof with another active agent such as a CDK inhibitor, including a CDK4 / 6 inhibitor, to treat a disorder mediated by the estrogen receptor, as described in more detail herein.

This invention provides estrogen receptor modulators having the structure (I), wherein R1, R2, R3, R4, Q, n, R8, R9, R10, and R11 have been defined in the specification; or a pharmaceutically acceptable salt thereof. The invention further provides methods for the preparation and use of the compounds.

Disclosed are furo[3,2-g]chromene derivatives represented by formula (I), stereoisomers, pharmaceutically acceptable salts, and pharmaceutical compositions thereof, as well as uses thereof as estrogen receptor modulators.

The present invention relates to a benzopiperidine derivative, a preparation method thereof and a medical use thereof. In particular, the present invention relates to a benzopiperidine derivative as shown by general formula (I), a preparation method thereof and a pharmaceutical composition containing the derivative, as well as a use thereof as an estrogen receptor modulator in the prevention and / or treatment of estrogen receptor-mediated or dependent diseases or conditions. Preferably, the disease is breast cancer. The substituents in the general formula (I) are the same as those defined in the description.

The present invention relates to a piperidine derivative and the preparation method and a pharmaceutical use thereof. In particular, the present invention relates to the piperidine derivative as shown by general formula (I) and the preparation method thereof and a pharmaceutical composition containing the same, and the use thereof as an estrogen receptor modulator in the treatment of estrogen receptor mediated or dependent diseases or conditions, the diseases preferably being breast cancer. In the abstract, the definition of each substituent of the general formula (I) is the same as that in the description.

The present invention is directed to pharmaceutical formulations and tablet compositions of pharmacological active agents of Formula (I) that are estrogen receptor modulators, and preparative processes thereof.